Sodium/Proton exchanger 3 in the medulla oblongata and set point of breathing control.

Rationale: In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in chemosensitive neurons of the ventrolateral brainstem augments central respiratory drive in anesthetized rabbits.

Objectives: To further explore the possible role of this exchanger for the control of breathing, we examined the individual relationship between brainstem NHE3 abundance and ventilation in rabbits during wakefulness.

Methods: In 32 adult male rabbits on standard nutritional alkali load, alveolar ventilation, metabolic CO2 production, and blood gases were determined, together with arterial and urinary acid-base status and renal base control functions. Expression of NHE3 in brainstem tissue from the obex region was determined by quantitative real-time reverse-transcription polymerase chain reaction analysis.

Measurements And Main Results: Regarding the distribution above and below the median, we classified high and low brainstem NHE3 animals, expressing a mean (+/- SEM) NHE3 mRNA of 2.08 +/- 0.28 and 0.72 +/- 0.06 fg cDNA/mg RNA, respectively. Alveolar ventilation of high brainstem NHE3 animals was lower than that of low brainstem NHE3 animals (715 +/- 36 vs. 919 +/- 41 ml . minute(-1); p < 0.01), a finding also reflected by a marked difference in Pa(CO2) (5.24 +/- 0.16 vs. 4.44 +/- 0.15 kPa; p < 0.01). Among possible secondary factors, CO2 production, systemic base excess, and fractional renal base reabsorption were not found to be different.

Conclusions: We conclude that the level of brainstem NHE3 expression-most likely via intracellular pH modulation-contributes to the individual control of breathing and Pa(CO2) in conscious rabbits by adjusting the set point and the loop gain of the system.